Proteolysis of von Willebrand factor (vWF) normally occurs through the action of a plasma enzyme that has recently been characterized; it accounts for the small quantities of cleavage products normally present in the circulation, and its inhibition can lead to the disease called thrombotic thrombocytopenic purpura (TTP). We have developed a rapid assay to evaluate the cleavage of vWF and have characterized patients with a TTP-like syndrome to detect those with low vWF cleaving protease activity. The assay does not require specialized reagents and can be completed within 6-8 hours on patient plasma. We studied a group of 50 masked plasmapheresis samples in collaboration with hematology investigators from UNC medical school and shown correlation with clinical status and with another assay for the protease. We have begun a collaboration with Dr. Anita Aggarwal to assess the response to plasma exchange and have a collaboration with Dr. William Stetler-Stevenson (NCI) to attempt to express the protein in mammalian cells.